Effect of CYP2D6 and CYP2C19 genotypes on atomoxetine serum levels: A study based on therapeutic drug monitoring data

阿托莫西汀 CYP2C19型 CYP2D6型 基因型 治疗药物监测 基因分型 药理学 医学 内科学 药代动力学 生物 遗传学 注意缺陷多动障碍 基因 精神科 哌醋甲酯
作者
Robert L. Smith,Espen Molden,Jean‐Paul Bernard
出处
期刊:British Journal of Clinical Pharmacology [Wiley]
卷期号:89 (7): 2246-2253 被引量:5
标识
DOI:10.1111/bcp.15706
摘要

Aims Atomoxetine is mainly metabolized by CYP2D6 while CYP2C19 plays a secondary role. It is known that patients carrying genotypes encoding decreased/absent CYP2D6 metabolism obtain higher atomoxetine concentrations and are at increased risk of adverse effects. Here, we aimed to investigate the added effects of reduced-function CYP2C19 genotype on atomoxetine concentrations in real-world settings. Methods Serum atomoxetine concentrations and CYP2D6/2C19 genotypes were included from a therapeutic drug monitoring service. Patients were first subgrouped according to CYP2D6 encoding normal, reduced or absent CYP2D6 metabolism, referred to as normal (NM), intermediate (IM) or poor metabolizers (PM). Then, the effect of reduced-function CYP2C19 genotypes was investigated. Genotyping of the CYP2D6 nonfunctional or reduced variant alleles comprised CYP2D6*3-*6, *9-*10 and *41. For CYP2C19, the CYP2C19*2 was analysed to define metabolizer phenotype. Dose-adjusted serum atomoxetine concentration was the exposure measure. Results Using a patient cohort (n = 315), it was found that CYP2D6 IM and PM patients had 1.9-fold (95% confidence interval: 1.4–2.7) and 9.6-fold (5.9–16) higher exposure of atomoxetine compared with CYP2D6 NMs. CYP2C19*2 carriers had 1.5-fold (1.1–2.2) higher atomoxetine exposure than noncarriers regardless of CYP2D6 genotype. Conclusion CYP2D6 genotype has a great impact on atomoxetine exposure, where our real-world data suggest atomoxetine dose requirements to be around half and 1/10 in CYP2D6 IM and PM vs. NM patients, respectively. When adding CYP2C19 genotype as a factor of relevance for personalized atomoxetine dosing, CYP2C19*2 carriers should further reduce the dose by a third. These findings suggest that pre-emptive CYP2D6/CYP2C19 genotyping should be performed to individualize atomoxetine dosing and prevent adverse effects.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
1秒前
2秒前
2秒前
3秒前
JamesPei应助Tethys采纳,获得10
3秒前
4秒前
4秒前
一洼清泉发布了新的文献求助30
5秒前
6秒前
111111发布了新的文献求助10
6秒前
智慧爷爷发布了新的文献求助10
7秒前
房幼枫发布了新的文献求助10
7秒前
8秒前
文艺书雪完成签到 ,获得积分10
8秒前
8秒前
今后应助科研狗采纳,获得10
9秒前
9秒前
爆米花应助樱桃窝窝头采纳,获得10
10秒前
LaTeXer应助magic_sweets采纳,获得50
11秒前
11秒前
11秒前
12秒前
智慧爷爷完成签到,获得积分10
13秒前
Meima完成签到,获得积分10
13秒前
叶春曼发布了新的文献求助10
14秒前
15秒前
xxxllllll发布了新的文献求助10
15秒前
房幼枫完成签到,获得积分10
15秒前
一颗肉丸完成签到 ,获得积分10
15秒前
碗碗关注了科研通微信公众号
15秒前
16秒前
16秒前
17秒前
科研通AI2S应助hf采纳,获得10
17秒前
Re发布了新的文献求助20
17秒前
甜蜜的阿飞完成签到,获得积分10
17秒前
雪白傲薇完成签到 ,获得积分20
18秒前
那咋了发布了新的文献求助10
20秒前
20秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3988827
求助须知:如何正确求助?哪些是违规求助? 3531197
关于积分的说明 11252739
捐赠科研通 3269830
什么是DOI,文献DOI怎么找? 1804815
邀请新用户注册赠送积分活动 881915
科研通“疑难数据库(出版商)”最低求助积分说明 809028